The overall aim of this project is to use genetic and molecular approaches to define the functions that the various type 12 E1 proteins play in transforming mouse and rat cells in vitro, and to understand the basis for the striking differences in viral oncogenicity between this serotype and non-oncogenic type 5.
Our specific aims over the next three years are: 1) To extend genetic and biochemical characterization of the host-range (hr) mutants of type 12 which we have recently isolated. 2) To isolate and characterize conditional transformation-defective mutants of this serotype. 3) To isolate and characterize site-specific mutants of type 12, particularly those which alter E1A mRNA splice junctions. 4) To isolate type 12 transformants of A549 cells. 5) To analyze the transformation process in mouse kidney cells, and determine if epithelial and fibroblastic subpopulations are transformed at different frequencies. 6) Extend our study of viral oncogenicity and cellular malignancy by testing the ability of hr mutants to induce tumors and tumor specific transplantation immunity. 7) Using type 12 hr mutants, develop a complementing system for isolation and growth of non-conditionally defective mutants.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA032940-05
Application #
3170821
Study Section
Virology Study Section (VR)
Project Start
1982-08-01
Project End
1988-07-31
Budget Start
1986-08-01
Budget End
1987-07-31
Support Year
5
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Carnegie-Mellon University
Department
Type
Schools of Arts and Sciences
DUNS #
052184116
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Williams, J F; Zhang, Y; Williams, M A et al. (2004) E1A-based determinants of oncogenicity in human adenovirus groups A and C. Curr Top Microbiol Immunol 273:245-88
Williams, J; Williams, M; Liu, C et al. (1995) Assessing the role of E1A in the differential oncogenicity of group A and group C human adenoviruses. Curr Top Microbiol Immunol 199 ( Pt 3):149-75
Telling, G C; Perera, S; Szatkowski-Ozers, M et al. (1994) Absence of an essential regulatory influence of the adenovirus E1B 19-kilodalton protein on viral growth and early gene expression in human diploid WI38, HeLa, and A549 cells. J Virol 68:541-7
Telling, G C; Williams, J (1994) Constructing chimeric type 12/type 5 adenovirus E1A genes and using them to identify an oncogenic determinant of adenovirus type 12. J Virol 68:877-87
Lamberti, C; Williams, J (1990) Differential requirement for adenovirus type 12 E1A gene products in oncogenic transformation. J Virol 64:4997-5007
Byrd, P J; Grand, R J; Breiding, D et al. (1988) Host range mutants of adenovirus type 12 E1 defective for lytic infection, transformation, and oncogenicity. Virology 163:155-65
Breiding, D E; Edbauer, C A; Tong, J Y et al. (1988) Isolation and characterization of adenovirus type 12 E1 host-range mutants defective for growth in nontransformed human cells. Virology 164:390-402
Edbauer, C; Lamberti, C; Tong, J et al. (1988) Adenovirus type 12 E1B 19-kilodalton protein is not required for oncogenic transformation in rats. J Virol 62:3265-73
Eager, K B; Williams, J; Breiding, D et al. (1985) Expression of histocompatibility antigens H-2K, -D, and -L is reduced in adenovirus-12-transformed mouse cells and is restored by interferon gamma. Proc Natl Acad Sci U S A 82:5525-9